Generation of an induced pluripotent stem cell line (CSBZZUi001-A) from a female Alzheimer's patient carrying the PSEN1 709 T > C heterozygous mutation.

Pluripotent stem cells were generated through the electroporation of episomal plasmids, containing crucial reprogramming factors, into skin fibroblasts extracted from a female Alzheimer's patient harboring the PSEN1 709 T > C (p.Phe237Leu) heterozygous mutation. The pluripotent stem cells exhibit a normal karyotype and express pivotal stem cell markers including TRA-1-60, Nanog, SOX2, and OCT4. Furthermore, their capacity to differentiate into the three germ layers in in vivo teratoma experiments has been substantiated. The pluripotent stem cell line can serve as a cellular model for Alzheimer's disease, offering significant value in elucidating the pathogenesis and therapeutic strategies of the disease.

Prognostic nomograms for elderly patients with small cell lung cancer brain metastasis: a SEER population-based study with temporal external validation.

OBJECTIVE: This study aimed to pinpoint independent predictors influencing overall survival (OS) and cancer-specific survival (CSS) in elderly patients with small cell lung cancer (SCLC) brain metastasis (BM), and to create and validate nomograms for OS and CSS prediction. METHODS: Data from elderly SCLC BM patients were extracted out of the SEER database, including 1200 patients identified from 2010 and 2015 who were randomly allocated into a training set and an internal validation set at a proportion of 7:3, and 666 patients diagnosed between 2018 and 2020 as a temporal external validation set. Independent predictors for OS and CSS were determined through univariate Cox analysis, least absolute shrinkage and selection operator (LASSO) analysis, and multivariate Cox analysis sequentially. Nomograms for OS and CSS were constructed, and validated by the internal and temporal external validation sets. RESULTS: Age, N stage, chemotherapy, and liver metastasis were determined as independent predictors of OS and CSS, while radiotherapy and surgery were not. Nomograms were constructed based on these independent predictors. The results of the receiver operator characteristic (ROC) curves, the areas under the curve (AUC) and calibration curve demonstrated that the nomograms exhibited commendable discriminative ability and calibration. Moreover, decision curve analysis (DCA), net reclassification improvement (NRI), and integrated discrimination improvement (IDI) also suggested that the nomograms possessed superior clinical usefulness and predictive capability relative to the TNM system. CONCLUSIONS: Prognostic nomograms for elderly patients with SCLC BM have been developed, demonstrating good performance in terms of accuracy, reliability, and practicality.

Individualized dynamic frailty-tailored therapy (DynaFiT) in elderly patients with newly diagnosed multiple myeloma: a prospective study.

It remains a substantial challenge to balance treatment efficacy and toxicity in geriatric patients with multiple myeloma (MM), primarily due to the dynamic nature of frailty. Here, we conducted a prospective study to evaluate the feasibility and benefits of dynamic frailty-tailored therapy (DynaFiT) in elderly patients. Patients with newly diagnosed MM (aged ≥ 65 years) received eight induction cycles of bortezomib, lenalidomide, and dexamethasone (daratumumab was recommended for frail patients), with treatment intensity adjusted according to longitudinal changes in the frailty category (IMWG-FI) at each cycle. Of 90 patients, 33 (37%), 16 (18%), and 41 (45%) were fit, intermediate fit, and frail at baseline, respectively. Of 75 patients who had geriatric assessment at least twice, 28 (37%) experienced frailty category changes at least once. At analysis, 15/26 (58%) frail patients improved (27% became fit and 31% became intermediate fit), 4/15 (27%) intermediate fit patients either improved or deteriorated (two for each), and 6/30 (20%) fit patients deteriorated. During induction, 34/90 (38%) patients discontinued treatment, including 10/33 (30%) fit, 4/16 (25%) intermediate fit, and 20/41 (49%) frail; 14/40 (35%) frail patients discontinued treatment within the first two cycles, mainly because of non-hematologic toxicity (mostly infections). For fit, intermediate-fit, and frail patients, the overall response rate was 100%, 93%, and 73%, respectively; one-year overall survival was 90%, 75%, and 54%, respectively. Therefore, the individualized DynaFiT is feasible and promising for heterogeneous elderly patients.

Capturing ammonium nitrate in a synthetic uranium oxide hydrate phase: revealing the role of ammonium ions and anion inclusions.

Although uranium oxide hydrate (UOH) minerals and synthetic phases have been extensively studied, the role of ammonium ions in the formation of UOH materials is not well understood. In this work, the stabilization of a synthetic UOH phase with ammonium ions and the inclusion of ammonium nitrate were investigated using a range of structural and spectroscopic techniques. Compound (NH4)2(NO3)[(UO2)3O2(OH)3] (U-N1) crystallises in the orthorhombic Pmn21 space group, having a layered structure with typical α-U3O8 type layers and interlayer (NH4)+ cations as well as (NO3)- anions. The presence of uranyl, (NH4)+ cations and (NO3)- anions were further confirmed with a combination of FTIR and Raman spectroscopies through characteristic vibrational modes. The roles of the (NH4)+ cations for charge compensation and facilitating the inclusion of (NO3)- anions via hydrogen bonding were revealed and discussed. The findings have implications for uranium geochemistry, reprocessing of spent nuclear fuel and possible spent nuclear fuel alteration pathways under geological disposal.

Investigation of Antibody Tolerance in Methanol for Analytical Purposes: Methanol Effect Patterns and Molecular Mechanisms.

The extraction of targets from biological samples for immunoassays using organic solvents, such as methanol, is often necessary. However, high concentrations of organic solvents in extracts invariably lead to instability of the employed antibody, resulting in poor performance of the immunoassay. Evaluating the tolerance ability and exploring the molecular mechanisms of antibody tolerance in organic solvents are essential for the development of robust immunoassays. In this work, 25 monoclonal antibodies and methanol are utilized as models to address these questions. A novel protocol is initially established to precisely and rapidly determine antibody tolerance in methanol, identifying two distinct methanol effect patterns. Through a detailed investigation of the structural basis, a novel hypothesis regarding methanol effect patterns is proposed, termed "folding-aggregation," which is subsequently validated through molecular dynamics simulations. Furthermore, the investigation of sequence basis reveals significant differences in residue types within the complementarity-determining regions and ligand-binding residues, distinguishing the two antibody methanol effect patterns. Moreover, the methanol effect patterns of the antibodies are defined by germline antibodies. This work represents the first exploration of antibody methanol effect patterns and associated molecular mechanisms, with potential implications for the discovery and engineering of tolerant antibodies for the development of robust immunoassays.

Ischemic cardio-cerebrovascular disease and all-cause mortality in Chinese elderly patients: a propensity-score matching study.

BACKGROUND: Ischemic cardio-cerebrovascular disease is the leading cause of mortality worldwide. However, studies focusing on elderly and very elderly patients are scarce. Hence, our study aimed to characterize and investigate the long-term prognostic implications of ischemic cardio-cerebrovascular diseases in elderly Chinese patients. METHODS: This retrospective cohort study included 1026 patients aged ≥ 65 years who were categorized into the mono ischemic cardio-cerebrovascular disease (MICCD) (either coronary artery disease or ischemic stroke/transient ischemic attack) (n = 912) and the comorbidity of ischemic cardio-cerebrovascular disease (CICCD) (diagnosed with both coronary artery disease and ischemic stroke/transient ischemic attack at admission) (n = 114). The primary outcome was all-cause death. The mortality risk was evaluated using the Cox proportional hazards risk model with multiple adjustments by conventional and propensity-score-based approaches. RESULTS: Of the 2494 consecutive elderly patients admitted to the hospital, 1026 (median age 83 years [interquartile range]: 76.5-86.4; 94.4% men) met the inclusion criteria. Patients with CICCD consisted mostly of very elderly (79.2% vs. 66.1%, P < 0.001) individuals with a higher burden of comorbidities. Over a median follow-up of 10.4 years, 398 (38.8%) all-cause deaths were identified. Compared with the MICCD group, the CICCD group exhibited a higher adjusted hazard ratio (HR) (95% confidential interval, CI) of 1.71 (1.32-2.39) for long-term mortality after adjusting for potential confounders. The sensitivity analysis results remained robust. After inverse probability of treatment weighting (IPTW) modeling, the CICCD group displayed an even worse mortality risk (IPTW-adjusted HR: 2.07; 95% CI 1.47-2.90). In addition, anemia (adjusted HR: 1.48; 95% CI 1.16-1.89) and malnutrition (adjusted HR: 1.43; 95% CI 1.15-1.78) are also independent risk factors for all-cause mortality among elderly and very elderly patients. CONCLUSIONS: Our results thus suggest that elderly patients with ischemic cardio-cerebrovascular disease and anemia or malnutrition may have higher mortality, which may be predicted upon admission. These findings, however, warrant further investigation.

Metal-Organic-Framework-Derived Nitrogen-Doped Carbon-Matrix-Encapsulating Co0.5Ni0.5 Alloy as a Bifunctional Oxygen Electrocatalyst for Zinc-Air Batteries.

The development of low-cost, high-performance oxygen electrocatalysts is of great significance for energy conversion and storage. As a potential substitute for precious metal electrocatalysts, the construction of efficient and cost-effective oxygen electrocatalysts is conducive to promoting the widespread application of zinc-air batteries. Herein, CoxNiyMOF nanoparticles encapsulated within a carbon matrix were synthesized and employed as cathode catalysts in zinc-air batteries. Co0.5Ni0.5MOF exhibits superior oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) performance and durability. The zinc-air battery assembled with Co0.5Ni0.5MOF as the air cathode exhibits a maximum power density of 138.6 mW·cm-2. These improvements are mainly attributed to the optimized metal composition of the cobalt-nickel alloy, which increases the specific surface area of the material and optimizes its pore structure. Significantly, the optimization of the electronic structure and active sites within the material has led to amplified ORR/OER activity and better zinc-air battery performance. This study underscores the immense promise of Co0.5Ni0.5MOF catalysts as feasible substitutes for commercial Pt/C catalysts in zinc-air batteries.

Factor XII and prekallikrein promote microvascular inflammation and psoriasis in mice.

BACKGROUND AND PURPOSE: Psoriasis is an autoimmune inflammatory skin disease, featuring microvascular abnormalities and elevated levels of bradykinin. Contact activation of Factor XII can initiate the plasma kallikrein-kinin cascade, producing inflammation and angioedema. The role of Factor XII in psoriasis is unknown. EXPERIMENTAL APPROACH: The effects of deficiency of Factor XII or its enzymatic substrate, prekallikrein, were examined in the imiquimod-induced mouse model of psoriasis. Skin microcirculation was assessed using intravital confocal microscopy and laser Doppler flowmeter. A novel antibody blocking Factor XII activation was evaluated for psoriasis prevention. KEY RESULTS: Expression of Factor XII was markedly up-regulated in human and mouse psoriatic skin. Genetic deletion of Factor XII or prekallikrein, attenuated imiquimod-induced psoriatic lesions in mice. Psoriatic induction increased skin microvascular blood perfusion, causing vasodilation, hyperpermeability and angiogenesis. It also promoted neutrophil-vascular interaction, inflammatory cytokine release and enhanced Factor XII / prekallikrein enzymatic activity with elevated bradykinin. Factor XII or prekallikrein deficiency ameliorated these microvascular abnormalities and abolished bradykinin increase. Antagonism of bradykinin B2 receptors reproduced the microvascular protection of Factor XII / prekallikrein deficiency, attenuated psoriatic lesions, and prevented protection by Factor XII / prekallikrein deficiency against psoriasis. Furthermore, treatment of mice with Factor XII antibody alleviated experimentally induced psoriasis and suppressed microvascular inflammation. CONCLUSION AND IMPLICATIONS: Activation of Factor XII promoted psoriasis via prekallikrein-dependent formation of bradykinin, which critically mediated psoriatic microvascular inflammation. Inhibition of contact activation represents a novel therapeutic strategy for psoriasis.

Inhibition of Prolactin Affects Epididymal Morphology by Decreasing the Secretion of Estradiol in Cashmere Bucks.

Yanshan Cashmere bucks are seasonal breeding animals and an important national genetic resource. This study aimed to investigate the involvement of prolactin (PRL) in the epididymal function of bucks. Twenty eleven-month-old Cashmere bucks were randomly divided into a control (CON) group and a bromocriptine (BCR, a prolactin inhibitor, 0.06 mg/kg body weight (BW)) treatment group. The experiment was conducted from September to October 2020 in Qinhuangdao City, China, and lasted for 30 days. Blood was collected on the last day before the BCR treatment (day 0) and on the 15th and 30th days after the BCR treatment (days 15 and 30). On the 30th day, all bucks were transported to the local slaughterhouse, where epididymal samples were collected immediately after slaughter. The left epididymis was preserved in 4% paraformaldehyde for histological observation, and the right epididymis was immediately preserved in liquid nitrogen for RNA sequencing (RNA-seq). The results show that the PRL inhibitor reduced the serum PRL and estradiol (E2) concentrations (p < 0.05) and tended to decrease luteinizing hormone (LH) concentrations (p = 0.052) by the 30th day, but no differences (p > 0.05) occurred by either day 0 or 15. There were no differences (p > 0.05) observed in the follicle-stimulating hormone (FSH), testosterone (T), and dihydrotestosterone (DHT) concentrations between the two groups. The PRL receptor (PRLR) protein was mainly located in the cytoplasm and intercellular substance of the epididymal epithelial cells. The PRL inhibitor decreased (p < 0.05) the expression of the PRLR protein in the epididymis. In the BCR group, the height of the epididymal epithelium in the caput and cauda increased, as did the diameter of the epididymal duct in the caput (p < 0.05). However, the diameter of the cauda epididymal duct decreased (p < 0.05). Thereafter, a total of 358 differentially expressed genes (DEGs) were identified in the epididymal tissues, among which 191 were upregulated and 167 were downregulated. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses revealed that ESR2, MAPK10, JUN, ACTL7A, and CALML4 were mainly enriched in the estrogen signaling pathway, steroid binding, calcium ion binding, the GnRH signaling pathway, the cAMP signaling pathway, and the chemical carcinogenesis-reactive oxygen species pathway, which are related to epididymal function. In conclusion, the inhibition of PRL may affect the structure of the epididymis by reducing the expression of the PRLR protein and the secretion of E2. ESR2, MAPK10, JUN, ACTL7A, and CALML4 could be the key genes of PRL in its regulation of epididymal reproductive function.

Knockdown of YTHDF2 initiates ERS-induced apoptosis and cancer stemness suppression by sustaining GLI2 stability in cervical cancer.

Cervical cancer ranks fourth in women in terms of incidence and mortality. The RNA-binding protein YTH N6-methyladenosine RNA-binding protein F2 (YTHDF2) contributes to cancer progression by incompletely understood mechanisms. We show how YTHDF2 controls the fate of cervical cancer cells and whether YTHDF2 could be a valid target for the therapy of cervical cancer. Sphere formation and alkaline phosphatase staining assays were performed to evaluate tumor stemness of cervical cancer cells following YTHDF2 knockdown. Apoptosis was detected by flow cytometry and TUNEL assay. The compounds 4PBA and SP600125 were used to investigate the correlation between JNK, endoplasmic reticulum stress, tumor stemness, and apoptosis. Data from The Cancer Genome Atlas (TCGA) databases and Gene Expression Omnibus (GEO) revealed that GLI family zinc finger 2 (GLI2) might be the target of YTHDF2. The transcription inhibitor actinomycin D and dual-luciferase reporter gene assays were employed to investigate the association between the GLI2 mRNA and YTHDF2. Nude mouse xenografts were generated to assess the effects of YTHDF2 knockdown on cervical cancer growth in vivo. Knockdown of YTHDF2 up-regulated the expression of GLI2, leading to JNK phosphorylation and endoplasmic reticulum stress. These processes inhibited the proliferation of cervical cancer cells and their tumor cell stemness and promotion of apoptosis. In conclusion, the knockdown of YTHDF2 significantly affects the progression of cervical cancer cells, making it a potential target for treating cervical cancer.

Personalized Nanovaccines Enhance Lymph Node Accumulation and Reprogram the Tumor Microenvironment for Improved Photodynamic Immunotherapy.

Tumor immunotherapy has emerged as an efficacious therapeutic approach that mobilizes the patient's immune system to achieve durable tumor suppression. Here, we design a photodynamic therapy-motivated nanovaccine (Dex-HDL/ALA-Fe3O4) co-delivering 5-aminolevulinic acid and Fe3O4 nanozyme that demonstrate a long-term durable immunotherapy strategy. After vaccination, the nanovaccine exhibits obvious tumor site accumulation, lymph node homing, and specific and memory antitumor immunity evocation. Upon laser irradiation, Dex-HDL/ALA-Fe3O4 effectively generates reactive oxygen species at the tumor site not only to induce the immunogenic cell death-cascade but also to trigger the on-demand release of full types of tumor antigens. Intriguingly, Fe3O4 nanozyme-catalyzed hydrogen peroxide generated oxygen for alleviating tumor hypoxia and modifying the inhibitory tumor microenvironment, thereby exhibiting remarkable potential as a sensitizer. The intravenous administration of nanovaccines in diverse preclinical cancer models has demonstrated remarkable tumor regression and inhibition of postoperative tumor recurrence and metastasis, thereby enabling personalized treatment strategies against highly heterogeneous tumors.

Exploring the Mechanism of Yiwei Decoction in the Intervention of a Premature Ovarian Insufficiency Rat Based on Network Pharmacology and the miRNA-mRNA Regulatory Network.

OBJECTIVE: our aim is to explore the mechanism of action of Yiwei decoction (YWD) in addressing premature ovarian insufficiency (POI) through a combination of transcriptomics and network pharmacology. By doing so, we hope to identify important pathways of action, key targets, and active components that contribute to the efficacy of YWD. MATERIALS AND METHODS: group A comprised of the model + traditional Chinese medicine group, while group B was the model control group and group C was the normal control group. After gavage, serum AMH and E2 levels were measured by using ELISA. HE staining was used to study the impact of YWD on ovarian follicle recovery in POI rats. Additionally, RNA-seq sequencing technology was employed to analyze the transcription levels of mRNAs and miRNAs in the ovarian tissues of each group, and the resulting data were examined using R. YWD used UPLC-Q-TOF-HRMS to analyze its active ingredients. Upon obtaining the sequencing results, the miRWalk database was utilized to forecast the targets of DEmiRNAs. Network pharmacology was then applied to predict the targets of active ingredients present in YWD, ultimately constructing a regulatory network consisting of active ingredients-mRNA-miRNA. The coexpression relationship between mRNAs and miRNAs was calculated using the Pearson correlation coefficient, and high correlation coefficients between miRNA-mRNA were confirmed through miRanda sequence combination. RESULTS: the application of YWD resulted in improved serum levels of AMH and E2, as well as an increased number of ovarian follicles in rats with POI. However, there was a minimal impact on the infiltration of ovarian lymphocytes. Through GSEA pathway enrichment analysis, we found that YWD may have a regulatory effect on PI3K-Akt, ovarian steroidogenesis, and protein digestion and absorption, which could aid in the treatment of POI. Additionally, our research discovered a total of 6 DEmiRNAs between groups A and B, including 2 new DEmiRNAs. YWD contains 111 active compounds, and our analysis of the active component-mRNA regulatory network revealed 27 active components and 73 mRNAs. Furthermore, the coexpression network included 5 miRNAs and 18 mRNAs. Our verification of MiRanda binding demonstrated that 12 of the sequence binding sites were stable. CONCLUSIONS: our research has uncovered the regulatory network mechanism of active ingredients, mRNA, and miRNA in YWD POI treatment. However, further research is needed to determine the effect of the active ingredients on key miRNAs and mRNAs.

Hydrogen doping control method for gasoline engine acceleration transient air-fuel ratio.

One of the primary contributors to automobile exhaust pollution is the significant deviation between the actual and theoretical air-fuel ratios during transient conditions, leading to a decrease in the conversion efficiency of three-way catalytic converters. Therefore, it becomes imperative to enhance fuel economy, reduce pollutant emissions, and improve the accuracy of transient control over air-fuel ratio (AFR) in order to mitigate automobile exhaust pollution. In this study, we propose a Linear Active Disturbance Rejection Control (LADRC) Hydrogen Doping Compensation Controller (HDC) to achieve precise control over the acceleration transient AFR of gasoline engines. By analyzing the dynamic effects of oil film and its impact on AFR, we establish a dynamic effect model for oil film and utilize hydrogen's exceptional auxiliary combustion characteristics as compensation for fuel loss. Comparative experimental results demonstrate that our proposed algorithm can rapidly regulate the AFR close to its ideal value under three different transient conditions while exhibiting superior anti-interference capability and effectively enhancing fuel economy.

Site-Specific Analysis of Core and Antenna Fucosylation on Serum Glycoproteins.

Fucosylation is an important structural feature of glycans and plays an essential role in the regulation of glycoprotein functions. Fucosylation can be classified into core- (CF) and antenna-fucosylation (AF, also known as (sialyl-) Lewis) based on the location on N-glycans, and they perform distinct biological functions. In this study, core- and antenna-fucosylated N-glycans on human serum glycoproteins that hold great clinical application values were systematically characterized at the site-specific level using StrucGP combined with the recently developed fucosylation assignment method. The results showed that fucosylation was widely distributed on serum glycoproteins, with 50% of fucosylated glycopeptides modified by AF N-glycans, 37% by CF N-glycans, and 13% by dual-fucosylated N-glycans. Interestingly, CF and AF N-glycans preferred to modify different groups of serum glycoproteins with different tissue origins and were involved in distinctive biological processes. Specifically, AF N-glycoproteins are mainly from the liver and participated in complement activation, blood coagulation, and endopeptidase activities, while CF N-glycoproteins originate from diverse tissues and are mainly involved in cell adhesion and signaling transduction. These data further enhanced our understanding of fucosylation on circulation glycoproteins.

Uranium Oxide Hydrate Frameworks with Dy(III) or Lu(III) Ions: Insights Into the Framework Structures With Lanthanide Ions.

Two uranium oxide hydrate frameworks (UOHFs) with either Dy3+ or Lu3+ ions, Dy1.36(H2O)6[(UO2)10UO13(OH)4] (UOHF-Dy) or Lu2(H2O)8[(UO2)10UO14(OH)3] (UOHF-Lu), were synthesized hydrothermally and characterized with a range of structural and spectroscopic techniques. Although SEM-EDS analysis confirmed the same atomic ratio of ~5.5 for U : Dy and U : Lu, they displayed different crystal morphologies, needles for UOHF-Dy in the orthorhombic C2221 space group and plates for UOHF-Lu in the triclinic P-1 space group. Both frameworks are composed of ß-U3O8 type layers linked by pentagonal bipyramidal uranium polyhedra, with the Dy3+/Lu3+ ions inside the channels. However, the arrangements of Dy3+/Lu3+ ions are different, with disordered Dy3+ ions well aligned at the centers of the channels and single Lu3+ ions well-separated in a zigzag pattern in the channels. While the characteristic vibrational modes were revealed by Raman spectroscopy, the presence of a pentavalent uranium center in UOHF-Lu was confirmed with diffuse reflectance spectroscopy. The formation of two types of UOHFs with lanthanide ions, high or low symmetry, and the structure trend were discussed regards to synthesis conditions and lanthanide ionic radius. This work highlights the complex chemistry driving the formation of UOHFs with lanthanide ions and has implications to the spent nuclear fuel under geological disposal.

Highly selective and sensitive immunoassays for flurogestone acetate analysis in goat milk: From rational hapten design and antibody production to assay development.

The preparation of high specificity and affinity antibodies is challenging due to limited information on characteristic groups of haptens in traditional design strategy. In this study, we first predicted characteristic groups of flurogestone acetate (FGA) using quantitative analysis of molecular surface combined with atomic charge distribution. Subsequently, FGA haptens were rationally designed to expose these identified characteristic groups fully. As a result, seven monoclonal antibodies were obtained with satisfactory performance, exhibiting IC50 values from 0.17 to 0.45 µg/L and negligible cross-reactivities below 1% to other 18 hormones. The antibody recognition mechanism further confirmed hydrogen bonds and hydrophobic interactions involving predicted FGA characteristic groups and specific amino acids in the antibodies contributed to their high specificity and affinity. Finally, one selective and sensitive ic-ELISA was developed for FGA determination with a detection limit as low as 0.12 µg/L, providing an efficient tool for timely monitoring of FGA in goat milk samples.

Effects of prolactin on the proliferation and hormone secretion of ovine granulosa cells in vitro.

Objective: The objective of this study was to investigate the effects of prolactin (PRL) on the proliferation and apoptosis of ovine ovarian granulosa cells (GCs) and the secretion of estrogen (E2) and progesterone (P4), as well as to explore the effects of PRL on related genes and proteins. Methods: We isolated ovarian GCs from 1-year-old small-tail Han sheep and identified PRL receptor (PRLR) on ovaries and follicle stimulating hormone receptor (FSHR) on ovarian GCs, respectively, using immunohistochemistry. PRL (0, 0.05, 0.50, 5.00 µg/mL) were added to GCs in vitro along with FSH, cell proliferation was measured by Cell Counting Kit-8 (CCK-8) and apoptosis by flow cytometry. The measurement of E2 and P4 content by ELISA after 24h and 48h. The expression of functional genes and proteins was identified by RT-qPCR and Western-blot after 24h. Results: PRLR was expressed in both follicular GCs and corpus luteum, whereas FSHR was expressed specifically. The proliferative activity was lower on day 1 while higher on day 4 and day 5. The apoptosis rate of GCs in the 0.05 µg/mL group was significantly higher than that in the control group after treatment with PRL for 24 h (p<0.05). Compared with the control group, the secretion of E2 in GCs was reduced significantly (p<0.05) in PRL treatment for 24h and 48h, while the secretion of P4 was significantly increased (p<0.05). The mRNA expression levels of PRLR, FSHR, LHR, CYP11A1, HSD3B7 and STAR were significantly higher than those in the control group (p<0.01), and the relative abundance of BCL2 in all PRL group were increased after PRL treatment. Conclusion: PRL promoted the proliferation of GCs and supraphysiological concentrations inhibited apoptosis caused by down-regulation of BAX and up-regulation of BCL2. PRL inhibited E2 by down-regulating CYP19A1 and promoted P4 by up-regulating CYP11A1, STAR and HSD3B7.